Funds are being requested for the purchase of an ABI PRISM 377 XL DNA Sequencer with 96-lane upgrade in order to upgrade and update the sequencing and genetic analysis capabilities of the Molecular Biotechnology Core laboratory at the Lerner Research Institute of the Cleveland Clinic Foundation. The acquisition of this state-of-the-art instrument that has a newly introduced 0.4 mm comb to enable 96-lane gel loading easier. It will empower the Core laboratory to extend its present services to include high throughput sequencing as well as microsatellite and mutational analysis that will impact on many research projects currently underway at the research Institute. At the present time DNA sequencing is the most widely used service offered by this Core facility and is often overtaxed in terms of ability to handle the large number of samples. In view of the rapid increase in the number of DNA sequencing samples received in 1998 and looking at the future projections, it is clear that we will require an additional sequencer with larger sample capacity. The high throughput runs using 96 lanes will allow us to dedicate one of the sequencers for microsatellite analysis and sizing DNA fragments. This would ensure that the investigators funded by the MH would be able to achieve their sequencing, genotyping and mutational analysis goals in a timely manner. The research investigators at the Cleveland Clinic are in a unique position, in that the close collaboration with the clinicians allow them access to patient material leading to identification of many clinically relevant diseases and syndromes. The ability to genotype individuals and families with disorders would aid in identifications of genes responsible paving way for possible therapeutic interventions. Similarly the ability to rapidly identify genetic mutations associated with disease states such as cancers by DNA sequencing will further our understanding of the causative mechanisms involved. The Lerner Research Institute is committed in providing effective state- of-the-art central core facilities to investigators. These Core laboratories are modem, well organized and run by trained and experienced personnel. This ensures that the instrumentation is serviced regularly and is made financially affordable to investigators who are then not required to use grant funding for redundant purchase or running of large equipment. The Institute has recently moved to the newly constructed Research and Education building which has permitted expansion in terms of space for hiring new principle investigators to expand on the existing departments or pioneer new ones. During this rapid expansion phase the demand for services such as sequencing, genotyping and mutation analysis is expected to increase significantly. The present DNA sequencing user group consists of staff scientists, postdoctoral fellows, graduate students and technical support personnel from over 60 PI laboratories funded through peer-reviewed NIH grants from both the basic and clinical departments. The addition a new DNA Sequencer with 96-lane capacity will significantly enhance the capability of this Core laboratory.